ELSPBP1

Summary

ELSPBP1 (epididymal sperm binding protein 1, HGNC:14417) is a protein-coding gene on chromosome 19q13.33, encoding Epididymal sperm-binding protein 1 (Q96BH3). Binds to spermatozoa upon ejaculation and may play a role in sperm capacitation.

The protein encoded by this gene belongs to the sperm-coating protein family of epididymal origin. This protein and its canine homolog are the first known examples of proteins with four tandemly arranged fibronectin type 2 (Fn2) domains in the Fn2-module protein family.

Source: NCBI Gene 64100 — RefSeq curated summary.

At a glance

• GWAS associations: 4
• Clinical variants (ClinVar): 29 total
• MANE Select transcript: NM_022142

Identifiers

Gene identifiers

Field	Value
HGNC ID	HGNC:14417
Approved symbol	ELSPBP1
Name	epididymal sperm binding protein 1
Location	19q13.33
Locus type	gene with protein product
Status	Approved
Aliases	HE12, E12, EDDM12
Ensembl gene	ENSG00000169393
Ensembl biotype	protein_coding
OMIM	607443
Entrez	64100

Gene structure

Transcript identifiers

Ensembl transcripts: 5 — 5 protein_coding

ENST00000339841, ENST00000593413, ENST00000593782, ENST00000596043, ENST00000597519

RefSeq mRNA: 1 — MANE Select: NM_022142 NM_022142

CCDS: CCDS12708

Canonical transcript exons

ENST00000339841 — 7 exons

Exon	Start	End
ENSE00001132353	48019719	48019877
ENSE00001132362	48015893	48016039
ENSE00001132367	48014171	48014308
ENSE00001132383	48022170	48022334
ENSE00001322533	48024952	48025154
ENSE00001347538	47994632	47994811
ENSE00001369015	48008651	48008737

Expression profiles

Bgee: expression breadth broad, 46 present calls, max score 99.78.

FANTOM5 (CAGE): breadth tissue_specific, TPM avg 0.4640 / max 692.4008, expressed in 28 samples.

FANTOM5 promoters (9 alternative TSS)

Promoter ID	TPM avg	Samples expressed
176739	0.1618	9
176737	0.0669	7
176742	0.0653	4
176743	0.0550	4
176741	0.0519	4
176738	0.0352	6
176740	0.0193	1
208880	0.0046	1
208881	0.0040	1

Top tissues by expression

243 total, by Bgee expression score (0-100, higher = more expressed):

Tissue	Anatomy ID	Expression score	Quality
corpus epididymis	UBERON:0004359	99.78	gold quality
cauda epididymis	UBERON:0004360	96.42	gold quality
male germ line stem cell (sensu Vertebrata) in testis	CL:0000089 ∩ UBERON:0000473	91.11	gold quality
caput epididymis	UBERON:0004358	79.06	gold quality
primordial germ cell in gonad	CL:0000670 ∩ UBERON:0000991	69.30	gold quality
tibialis anterior	UBERON:0001385	68.26	silver quality
gluteal muscle	UBERON:0002000	67.75	gold quality
triceps brachii	UBERON:0001509	67.67	gold quality
pancreatic ductal cell	CL:0002079	65.33	silver quality
sperm	CL:0000019	64.78	gold quality
buccal mucosa cell	CL:0002336	62.77	gold quality
cervix squamous epithelium	UBERON:0006922	61.75	gold quality
ileal mucosa	UBERON:0000331	60.43	silver quality
olfactory bulb	UBERON:0002264	60.10	gold quality
type B pancreatic cell	CL:0000169	59.89	gold quality
secondary oocyte	CL:0000655	59.70	gold quality
seminal vesicle	UBERON:0000998	58.93	gold quality
myocardium	UBERON:0002349	58.90	gold quality
deltoid	UBERON:0001476	58.81	silver quality
pigmented layer of retina	UBERON:0001782	57.58	silver quality
nasal cavity epithelium	UBERON:0005384	57.42	gold quality
decidua	UBERON:0002450	56.55	gold quality
tendon of biceps brachii	UBERON:0008188	56.40	gold quality
heart right ventricle	UBERON:0002080	55.31	gold quality
upper leg skin	UBERON:0004262	54.45	silver quality
quadriceps femoris	UBERON:0001377	53.81	gold quality
hair follicle	UBERON:0002073	52.43	gold quality
cerebellar vermis	UBERON:0004720	52.21	gold quality
cervix epithelium	UBERON:0004801	52.11	gold quality
vastus lateralis	UBERON:0001379	51.75	gold quality

Single-cell (SCXA)

Detected in 1 experiment(s), a significant marker in 1.

Experiment	Marker?	Max mean expression
E-ANND-3	yes	2.78

Regulation

Is transcription factor: no

miRNA regulators (miRDB)

8 targeting ELSPBP1, top 30 by miRDB confidence (max_score; target_count = how many genes the miRNA targets in total — lower means more specific):

miRNA	Max score	Avg score	miRNA target_count
HSA-MIR-6873-3P	100.00	71.42	2626
HSA-MIR-4799-5P	99.82	70.60	2663
HSA-MIR-106A-3P	99.53	67.58	995
HSA-MIR-100-3P	99.20	67.33	672
HSA-MIR-876-3P	98.76	68.23	945
HSA-MIR-2467-3P	98.65	67.18	1969
HSA-MIR-6780A-3P	98.42	67.49	1518
HSA-MIR-6770-3P	88.39	62.36	71

Literature-anchored findings (GeneRIF, showing 4)

• Sperm-binding fibronectin type II-module proteins are genetically linked and functionally related. (PMID:17307309)
• characterize the assembly of a five-component complex containing TAL1, LMO2, Ldb1, E12, and DNA. The bHLH domains of TAL1 and E12 alone primarily formed helical homodimers, but together formed heterodimers, to which LMO2 bound with high affinity (PMID:17910069)
• These biochemical and functional data reveal RANBP16 and RANBP17 as novel regulators of E2A protein action, and demonstrate specific interaction of E12 with RANBP17. (PMID:20503194)
• HCV core protein represses E-cadherin expression by upregulating E12/E47 levels to induce EMT in HCV-associated HCC. (PMID:25817725)

Cross-species orthologs

0 orthologs

Paralogs (1): BSPH1 (ENSG00000188334)

Protein

Protein identifiers

Epididymal sperm-binding protein 1 — Q96BH3 (reviewed: Q96BH3)

Alternative names: Epididymal secretory protein 12

All UniProt accessions (6): A0A384NKL6, Q96BH3, M0QZH6, M0R006, M0R179, M0R331

UniProt curated annotations — full annotation on UniProt →

Function. Binds to spermatozoa upon ejaculation and may play a role in sperm capacitation. Has phosphorylcholine-binding activity.

Subcellular location. Secreted.

Tissue specificity. Detected in cauda epididymidal fluid and on sperm membrane (at protein level).

Post-translational modifications. N-glycosylated.

Similarity. Belongs to the seminal plasma protein family.

RefSeq proteins (1): NP_071425* (*=MANE)

Domains & families (InterPro)

ID	Name	Type
IPR000562	FN_type2_dom	Domain
IPR013806	Kringle-like	Homologous_superfamily
IPR036943	FN_type2_sf	Homologous_superfamily
IPR051666	SP_Capacitation_Regulator	Family

Pfam: PF00040

UniProt features (19 total): disulfide bond 6, sequence variant 4, domain 4, sequence conflict 2, signal peptide 1, chain 1, glycosylation site 1

Structure

Experimental structures (PDB)

0 structures.

Predicted structure (AlphaFold)

Model	pLDDT	Fraction very-high
AF-Q96BH3-F1	84.26	0.62

Functional residue map

Curated UniProt residues grouped by drug-discovery relevance — catalytic, ligand-binding, modification, and mutation-validated positions. Source: UniProtKB sequence features.

Disulfide bonds (6): 143–168, 182–208, 196–223, 74–100, 88–115, 129–153

Glycosylation sites (1): 195

Function

Pathways and Gene Ontology

Reactome pathways

0 pathways

MSigDB gene sets: 43 (showing top): GSE45365_CD8A_DC_VS_CD11B_DC_IFNAR_KO_MCMV_INFECTION_DN, GOBP_SINGLE_FERTILIZATION, GOCC_CELL_SURFACE, GOBP_MALE_GAMETE_GENERATION, GOBP_SPERM_CAPACITATION, GOBP_ANATOMICAL_STRUCTURE_MATURATION, BLALOCK_ALZHEIMERS_DISEASE_UP, GOBP_CELL_MATURATION, GOBP_CELLULAR_PROCESS_INVOLVED_IN_REPRODUCTION_IN_MULTICELLULAR_ORGANISM, GOMF_GLYCOSAMINOGLYCAN_BINDING, GOBP_DEVELOPMENTAL_PROCESS_INVOLVED_IN_REPRODUCTION, GOBP_FERTILIZATION, GOMF_HEPARIN_BINDING, MODULE_69, GOMF_SULFUR_COMPOUND_BINDING

GO Biological Process (2): single fertilization (GO:0007338), sperm capacitation (GO:0048240)

GO Molecular Function (1): heparin binding (GO:0008201)

GO Cellular Component (2): extracellular region (GO:0005576), cell surface (GO:0009986)

GO top-level categories

Rollup of top GO terms by namespace:

Category	Terms
cellular anatomical structure	2
fertilization	1
developmental process involved in reproduction	1
spermatid development	1
cellular process involved in reproduction in multicellular organism	1
cell maturation	1
glycosaminoglycan binding	1
sulfur compound binding	1

Protein interactions and networks

STRING

756 interactions, top by confidence (×1000):

Protein A	Protein B	Partner UniProt	Score
ELSPBP1	BLVRA	P53004	680
ELSPBP1	CCNA2	P20248	547
ELSPBP1	CDK2	P24941	532
ELSPBP1	GLIPR1L1	Q6UWM5	520
ELSPBP1	CCNA1	P78396	511
ELSPBP1	TEX101	Q9BY14	494
ELSPBP1	TEDDM1	Q5T9Z0	492
ELSPBP1	ALB	P02768	469
ELSPBP1	CCND1	P24385	437
ELSPBP1	CCNE1	P24864	428
ELSPBP1	ZSWIM9	Q86XI8	417
ELSPBP1	CCNB1	P14635	415
ELSPBP1	PSMA6	P34062	408
ELSPBP1	ZPBP	Q9BS86	395
ELSPBP1	TIMP1	P01033	395

IntAct

4 interactions, top by confidence:

A	B	Type	Score
ELSPBP1	PFDN1	psi-mi:“MI:0914”(association)	0.530
ELSPBP1	QSOX1	psi-mi:“MI:0914”(association)	0.350
ELSPBP1	ADAM10	psi-mi:“MI:0914”(association)	0.350

BioGRID (101): ELSPBP1 (Reconstituted Complex), ELSPBP1 (Protein-peptide), OLIG1 (Affinity Capture-Western), OLIG2 (Affinity Capture-Western), FKBP14 (Affinity Capture-MS), PFDN5 (Affinity Capture-MS), PFDN1 (Affinity Capture-MS), ZNF703 (Affinity Capture-MS), MICA (Affinity Capture-MS), KDELC1 (Affinity Capture-MS), NPTX1 (Affinity Capture-MS), FBLN1 (Affinity Capture-MS), TUBB8 (Affinity Capture-MS), EDEM2 (Affinity Capture-MS), RTCA (Affinity Capture-MS)

ESM2 similar proteins: A4K2P0, A5X2X1, A7X3V7, B2BRQ6, B2BS84, E5AJX3, F6ULY1, I2G9B4, O35536, O43278, O43291, O55006, O89103, P00974, P00992, P02784, P04557, P13385, P17945, P26461, P48307, P51864, P51865, P80964, P81019, P81121, Q075Z2, Q08048, Q08E66, Q0Q236, Q16609, Q3UW26, Q5RCS3, Q6UW32, Q76BS1, Q7SXB3, Q7TMJ8, Q7YR83, Q867B7, Q8TEU8

Diamond homologs: A4KX75, D0EM77, D3ZTE0, G5EBU3, G5EGM1, O04529, O18733, O23507, O35548, O44836, O54732, O55761, O60449, O75900, O88272, O88676, O97507, P00748, P02751, P04937, P07589, P08169, P08253, P09237, P11276, P11717, P11722, P14780, P22757, P22897, P24347, P28053, P29136, P33434, P33436, P41245, P41246, P49259, P49260, P50280

SIGNOR signaling

0 interactions.

Disease & clinical

Clinical variants and AI predictions

ClinVar

29 variants total. Per-class counts are floors (≥ shown; pagination cap):

Classification	Count (floor)
Pathogenic	0
Likely pathogenic	0
Uncertain significance	26
Likely benign	0
Benign	0

Top pathogenic / likely-pathogenic (0)

SpliceAI

1038 predictions. Top by Δscore:

Variant	Effect	Δscore
19:48019841:GA:G	donor_gain	1.0000
19:48019842:A:G	donor_gain	1.0000
19:48019847:G:GT	donor_gain	1.0000
19:48019852:A:T	donor_gain	1.0000
19:48019878:G:GG	donor_gain	1.0000
19:47994809:AAGG:A	donor_loss	0.9900
19:47994810:AGGTA:A	donor_loss	0.9900
19:47994811:GGTAC:G	donor_loss	0.9900
19:47994812:G:GA	donor_loss	0.9900
19:47994813:T:G	donor_loss	0.9900
19:48008649:A:AG	acceptor_gain	0.9900
19:48008650:G:GG	acceptor_gain	0.9900
19:48008650:GA:G	acceptor_gain	0.9900
19:48019840:GGA:G	donor_gain	0.9900
19:48019857:G:GT	donor_gain	0.9900
19:48008648:C:G	acceptor_gain	0.9800
19:48014169:A:AG	acceptor_gain	0.9800
19:48014169:AG:A	acceptor_gain	0.9800
19:48014170:G:GG	acceptor_gain	0.9800
19:48014170:GG:G	acceptor_gain	0.9800
19:48014170:GGGAT:G	acceptor_gain	0.9800
19:48015920:T:G	acceptor_gain	0.9800
19:48019851:G:GT	donor_gain	0.9800
19:48019855:G:GG	donor_gain	0.9800
19:48024949:A:AG	acceptor_gain	0.9800
19:48024949:AAG:A	acceptor_gain	0.9800
19:48024950:A:G	acceptor_gain	0.9800
19:48008733:TGGAG:T	donor_loss	0.9700
19:48008736:AGGT:A	donor_loss	0.9700
19:48008737:GGTAA:G	donor_loss	0.9700

AlphaMissense

1490 scored. Top likely-pathogenic:

Variant	Protein change	am_pathogenicity
19:48022211:T:C	F186L	0.983
19:48022213:C:A	F186L	0.983
19:48022213:C:G	F186L	0.983
19:48014197:T:C	F33L	0.975
19:48014199:C:A	F33L	0.975
19:48014199:C:G	F33L	0.975
19:48022276:G:C	W207C	0.973
19:48022276:G:T	W207C	0.973
19:48015916:T:C	F78L	0.970
19:48015918:C:A	F78L	0.970
19:48015918:C:G	F78L	0.970
19:48022277:T:A	C208S	0.969
19:48022278:G:C	C208S	0.969
19:48022206:T:G	F184C	0.968
19:48022281:C:A	A209E	0.962
19:48015981:G:C	W99C	0.958
19:48015981:G:T	W99C	0.958
19:48022205:T:C	F184L	0.955
19:48022207:T:A	F184L	0.955
19:48022207:T:G	F184L	0.955
19:48019820:T:A	C153S	0.954
19:48019821:G:C	C153S	0.954
19:48014191:T:C	F31L	0.951
19:48014193:T:A	F31L	0.951
19:48014193:T:G	F31L	0.951
19:48015982:T:A	C100S	0.950
19:48015983:G:C	C100S	0.950
19:48022324:C:G	C223W	0.950
19:48019819:G:C	W152C	0.947
19:48019819:G:T	W152C	0.947

dbSNP variants (sampled 300 via entrez): RS1000066264 (19:48024644 C>G), RS1000091717 (19:47994380 CT>CCAA,CTT), RS1000165395 (19:47994108 G>A), RS1000195071 (19:47994934 T>C), RS1000237138 (19:48021382 G>A), RS1000337942 (19:48001569 T>G), RS1000454914 (19:47993858 A>G), RS1000590067 (19:47994139 T>C), RS1000654595 (19:47998419 GA>G,GAA), RS1000671203 (19:48004156 C>T), RS1000765353 (19:48023293 G>A,T), RS1000786926 (19:48003810 T>A), RS1000836198 (19:48001889 G>A,T), RS1000896087 (19:48009336 T>A), RS1000901672 (19:47998602 C>A,G)

Disease associations

OMIM: gene MIM:607443 | disease phenotypes:

GenCC curated gene-disease

Mondo (0):

Orphanet (0):

HPO phenotypes

0 total (0 of 0 shown, HPO-id order):

GWAS associations

4 associations (top):

Study	Trait	p-value
GCST001428_16	Intelligence	2.000000e-06
GCST001428_5	Intelligence	3.000000e-08
GCST005926_5	Peak cortisol response to low dose short synacthen test in corticosteroid treated asthma	3.000000e-07
GCST010002_57	Refractive error	1.000000e-27

EFO canonical traits (3, from GWAS)

EFO ID	Trait name
EFO:0004337	intelligence
EFO:0005843	cortisol measurement
EFO:0009175	response to synacthen

Drugs & pharmacology

Drug and pharmacology data

Is drug target: no

PharmGKB: 1 entry (VIP=true, CPIC=false)

CTD chemical–gene interactions

5 total (human), top 5 by PubMed support.

Chemical	Actions (top 5)	PubMed papers
Atrazine	increases expression	1
Benzo(a)pyrene	decreases methylation, increases methylation, affects methylation	1
Cadmium	decreases expression, increases abundance	1
Tunicamycin	increases expression	1
Cadmium Chloride	decreases expression, increases abundance	1

Clinical trials (associated diseases)

0 trials via MONDO — disease-level, not drug-specific.